Cetuximab is associated with excessive toxicity when combined with bevacizumab Plus mFOLFOX6 in metastatic colorectal carcinoma

Abstract

Background: The bevacizumab-cetuximab combination has shown promising activity in chemotherapy-refractory metastatic colorectal cancer (mCRC). We sought to determine the safety and efficacy of cetuximab added to bevacizumab plus standard mFOLFOX6 (modified 5-fluorouracil [5-FU]/leucovorin/oxaliplatin) as first-line therapy for mCRC.

Patients and methods: Sixty-six patients received cetuximab (400 mg/m2 loading dose, then 250 mg/m2 weekly intravenously [I.V.]) plus bevacizumab 5 mg/kg and mFOLFOX6 chemotherapy every 2 weeks. The primary endpoint was toxicity.

Results: The most common grade 3-4 events included diarrhea (14%), fatigue (14%), neuropathy (12%), venous thrombosis (9%), acneiform rash (8%), and desquamation (8%). A protocol-defined prohibitive adverse event occurred in 4 patients (6%), including 2 treatment-associated deaths. Thirty-seven patients (56%) discontinued therapy before disease progression because of either toxicity (n = 19; 29%) or patient withdrawal (n = 18; 27%). Twenty-eight of 37 patients (76%) who discontinued therapy before disease progression did so because of cetuximab-associated toxicity.

Conclusion: Although the addition of cetuximab to bevacizumab plus mFOLFOX6 was not associated with excessive life-threatening toxicity, many patients discontinued therapy because of cetuximab-associated toxicity. Taken together with the results of recently reported phase III trials, cetuximab should not be used concurrently with bevacizumab and infusional 5-FU, leucovorin, and oxaliplatin chemotherapy for the treatment of mCRC.

Conflict of interest statement

Disclosures

Dr. Ocean is a member of the Speaker’s Bureau for Eli Lilly and Company, Genentech, Inc., and sanofi-aventis U.S. Dr. Polite is a member of the Speaker’s Bureau for sanofi-aventis U.S. Dr. Polite has received honoraria from sanofi-aventis U.S. Dr. Kindler has received research funding from Genentech, Inc. and served as a consultant for Roche and Genentech, Inc. Dr. Sparano has served as a consultant for Genentech and sanofi-aventis U.S. The remaining authors report no potential conflicts of interest.

Figures

Figure 1. Cumulative Toxicity by CTCAE Grade

This chart shows the frequency of adverse events occurring in at least 10% of patients (or any grade 3–4 event occurring in at least 1 patient). Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; CTCAE = Common Terminology Criteria for Adverse Events; NOS = not otherwise specified; SGOT = serum glutamic oxaloacetic transaminase; SGPT = serum glutamic pyruvic transaminase